Cyclosporine therapy for Langerhans cell histiocytosis.
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Biomedical subjects
Publications and source records attributed to J Tamura.
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A patient with chronic idiopathic thrombocytopenic purpura (ITP), chronic disseminated intravascular coagulation (DIC) and abdominal aortic aneurysm is described. He had severe thrombocytopenia and his platelet life span was shortened (29 h). Indium 111-labeled platelet scintigraphy demonstrated an increased accumulation of radioactivity over the aneurysm and the spleen. Following preoperative heparin therapy for DIC, the platelet count remained low (10 x 10(9)/l), while the DIC improved. Because of the elevated platelet-associated IgG, we considered that the patient had complicated chronic ITP. After intravenous immunoglobulin therapy, his platelet count increased. The aneurysm was successfully replaced with an artificial Y-graft vessel and a splenectomy was performed at the same time. The platelet count was maintained at about 60 x 10(9)/l after the operation and the patient is quite well now.
A rare case of non-Hodgkin's lymphoma (NHL) that showed transient spontaneous regression (SR) is described. After 6 months of remission, recurrence was noted in the lymph nodes, pleura and the spleen. Although transient improvement was observed following combination chemotherapy, the pleural effusion became refractory to chemotherapy and the patient died 9 months after the relapse.
A 70-year-old man was admitted to our hospital with pancytopenia. He was diagnosed as having MDS (RA), and therapy with subcutaneous S-CSF (100 micrograms/day) was started. His leukocyte count increased from 800/microliters to 1,400/microliters in two weeks. The dose of G-CSF was raised to 200 micrograms/day in the third week, and leukocytes increased to 2,00/microliters. At the fifth week, intravenous EPO (6,000 U x 3 times/week) was added. His leukocyte count increased to 4,000/microliters. EPO therapy was raised to 12,000 U x 3 times/week at the eighth week, his leukocyte count remained at the same level. G-CSF and EPO was stopped at the eleventh week, and leukocytes decreased to the same level as before administration. Throughout the course, his platelet count and reticulocyte count did not change. G-CSF and EPO are known as the stimulators of granuriod and erythroid progenitor, respectively. However, in this case, combination therapy with G-CSF and EPO induced marked increase of granulocytes only. This was an interesting case in relation to the roles of these cytokines in the hematopoietic system.
We studied the efficacy and safety of a combination therapy with sulbactam/cefoperazone (SBT/CPZ) and amikacin (AMK) on severe infections in the patients with hematological disorders. We administered SBT/CPZ and AMK to 65 patients and analyzed the result of 57 patients, except for 8 drop outs, for evaluation. The overall clinical efficacy of this combination therapy was 64.9% (excellent in 15 patients, good in 22 patients). Thirty seven patients had sepsis and suspected sepsis. The efficacy was 67.6% in these patients. The rate of improvement in the cases (18 patients) with neutrophil counts under 500/mm3 during the administration among 28 patients who had not responded to prior antibiotic treatment was 67.9%. Diarrhea was found in 1 patient as an apparent side effect likely related to this drug regimen. It appears that combination therapy of SBT/CPZ and AMK was a useful regimen in the treatment of infectious diseases complicated with hematological disorders.
A 28-year-old woman was admitted to our hospital with cough. CT scan indicated a huge mass in the anterior mediastinum. A transcutaneous needle biopsy showed tumor cell infiltration and compartmentalizing fibrosis. The tumor cells were positive for CD20 and CD45, and JH rearrangement was evident. The patient was diagnosed as mediastinal diffuse large-cell lymphoma with sclerosis. The tumor responded to combination chemotherapy. It should be emphasized that mediastinal diffuse large-cell lymphoma can be diagnosed using a small specimen obtained by transcutaneous needle biopsy.
Antigen recognition by the T-cell receptor (TCR) initiates events including lymphokine gene transcription, particularly interleukin-2, that lead to T-cell activation. The immunosuppressive drugs, cyclosporin A (CsA) and FK-506, prevent T-cell proliferation by inhibiting a Ca(2+)-dependent event required for induction of interleukin-2 transcription. Complexes of FK-506 or CsA and their respective intracellular binding proteins inhibit the calmodulin-dependent protein phosphatase, calcineurin, in vitro. The pharmacological relevance of this observation to immunosuppression or drug toxicity is undetermined. Calcineurin, although present in lymphocytes, has not been implicated in TCR-mediated activation of lymphokine genes or in transcriptional regulation in general. Here we report that transfection of a calcineurin catalytic subunit increases the 50% inhibitory concentration (IC50) of the immunosuppressants FK-506 and CsA, and that a mutant subunit acts in synergy with phorbol ester alone to activate the interleukin-2 promoter in a drug-sensitive manner. These results implicate calcineurin as a component of the TCR signal transduction pathway by demonstrating its role in the drug-sensitive activation of the interleukin-2 promoter.
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Electrospray ionization mass spectra of human hemoglobin chains and of transferrin were acquired on a magnetic sector mass spectrometer. The observed molecular ion for each hemoglobin chain was in good agreement with the theoretical isotopic distribution at a reasonable resolution of 2000. The clear separation of a variant beta-chain in admixture with the normal counterpart at mass 15,867 that differed from it by 14 Da (0.09%) ensured that a smaller mass difference could be detected. The molecular ions for human transferrin were too broad compared with the theoretical shape to determine the molecular mass accurately, probably due to the heterogeneity of the carbohydrate moiety. A decrease in mass by neuraminidase digestion, however, determined the average number of sialic acids in the molecule.
A 24-year-old Japanese male having ulcerative colitis and idiopathic thrombocytopenic purpura is described. When the symptoms of ulcerative colitis were manifest during his clinical course, the platelet life-span was shortened and the platelet associated IgG level was increased. Thus, causal association between the two diseases may be suggested.
The effect of three anticancer agents, cisplatin, doxorubicin, and mitomycin, on liver regeneration after 70% partial hepatectomy in rats was investigated by total DNA content of the liver and flow cytometric analysis of hepatocyte nuclei using two-color staining of anti-bromodeoxyuridine monoclonal antibody and propidium iodide. Total DNA content of regenerating liver 7 days after hepatectomy showed significant suppression of regeneration by these agents (P less than 0.01). The inhibitory effects of the agents on the cell cycle of hepatocytes by flow cytometric analysis were (1) a delay of the peak or a decrease in the proportion of S phase nuclei and/or (2) polyploidization of the nuclei, demonstrated by accumulation of 8c and occasionally 16c nuclei, of which the DNA contents were four and eight times as much as that of diploid (2c) cell nuclei, respectively. The former (1) suggests G0 or G1 phase block, and the latter (2) G2 phase block. In terms of total DNA content of regenerating liver, the inhibitory effect was most prominent in the cisplatin-administered groups. The polyploidization of nuclei was most remarkable in the mitomycin-administered groups. Although the total DNA content recovered to the level of control at 6 weeks after hepatectomy, the polyploidization effect persisted in the drug-administered groups. These agents had no cytocidal action on proliferating hepatocytes as can be seen from the aspartate aminotransferase and alanine aminotransferase serum levels. We conclude that in a short-term observation, the anti-cancer agents significantly inhibit liver regeneration, although the inhibitory effect on DNA synthesis does not last long.(ABSTRACT TRUNCATED AT 250 WORDS)
To clarify the mechanism of the intoxicating feeling attained after a traditional 47 degrees C hot-spring bath called 'jikan-yu' in Kusatsu-spa, Japan, we examined the change in plasma levels of beta-endorphin and methionine enkephalin in 7 healthy subjects. The mean sublingual temperature rose from 36.8 degrees C to 38.6 degrees C and the plasma beta-endorphin level from 16.2 pg/ml to 49.5 pg/ml 2 minutes after completing a 3-minute bath in 47 degrees C hot-spring water. However, the plasma methionine enkephalin level was not changed. This feeling of intoxication may be explained by the transient rise in plasma beta-endorphin level.
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The case of a 59-year-old Japanese woman with post-gastrectomy megaloblastic anaemia having urinary and faecal incontinence and paraesthesia in four extremities is described. While the haematological abnormalities were improved by administration of a total dose of 17 mg of intramuscular mecobalamin, the neurological abnormalities remained unchanged. Five months later, a total dose of 7.5 mg of mecobalamin was injected intravenously over a period of 5 weeks, although the serum level of vitamin B12 was greater than 1180 pmol l-1. Immediately after initiation of the therapy, the urinary and faecal incontinence were gradually improved, and were completely cured within 2 months. The peripheral neuropathy was also ameliorated. The effectiveness of intravenous vitamin B12 injection for the neurological abnormalities due to vitamin B12 deficiency is emphasized.